The majority of patients with multiple myeloma can be effectively palliated by the use of chemotherapy. However, a significant number of patients are resistant to initial therapy or relapse after treatment. Thus, there is a need for new agents with activity against the disease. Topotecan is a semisynthetic analog of camptothecin which incorporates a stable basic side-chain at the 9-position of the A-ring of 10 hydroxycamptothecin. The addition of this side-chain provides improved water solubility of the compound without requiring hydrolysis of the E-ring lactone. The study will evaluate the response rate for refractory myeloma treated with topotecan, the qualitative and quantitative toxicities of topotecan administered in a Phase II study and measure topoisomerase levels in multiple myeloma cells.